HIF-1α inhibition alleviates the exaggerated exercise pressor reflex in rats with peripheral artery disease induced by femoral artery occlusion

Hypoxia-inducible factor 1 alpha (HIF-1 alpha) is a transcription factor mediating adaptive responses to hypoxia and ischemia. Our previous work showed that HIF-1 alpha is increased in muscle sensory nerves of rats with peripheral artery disease (PAD) induced by femoral artery occlusion. The present study was further to examine the role played by HIF-1 alpha in regulating the response of arterial blood pressure (BP) to the activation of muscle afferent nerve during static muscle contraction in rats with femoral artery occlusion. A rat model of femoral artery ligation was used to study PAD in this study. Western blot analysis was employed to examine the protein levels of HIF-1 alpha in the dorsal root ganglion (DRG) tissues. BAY87, a synthesized compound with the characteristics of highly potent and specific suppressive effects on expression and activity of HIF-1 alpha, was given into the arterial blood supply of the ischemic hindlimb muscles before the exercise pressor reflex was evoked by static muscle contraction. First, HIF-1 alpha was increased in the DRG of occluded limbs (optical density: 0.89 +/- 0.13 in control versus 1.5 +/- 0.05 in occlusion; p < 0.05, n = 6 in each group). Arterial injection of BAY87 (0.2 mg/kg) then inhibited expression of HIF-1 alpha in the DRG of occluded limbs 3 hr following its injection (optical density: 1.02 +/- 0.09 in occluded limbs with BAY87 versus 1.06 +/- 0.1 in control limbs; p > 0.05, n = 5 in each group). In addition, muscle contraction evoked a greater increase in BP in occluded rats. BAY87 attenuated the enhanced BP response in occluded rats to a greater degree than in control rats. Our data suggest that the inhibition of HIF-1 alpha alleviates the exaggeration of the exercise pressor reflex in rats under ischemic circumstances of the hindlimbs in PAD induced by femoral artery occlusion.

Automated summary

This study investigated the role of HIF-1α in regulating the response of arterial blood pressure during muscle contraction in rats with femoral artery occlusion-induced PAD. The results suggest that inhibition of HIF-1α alleviates the exaggeration of the exercise pressor reflex in rats under ischemic circumstances, indicating a potential therapeutic target for PAD.